The explicit goal of this Project is to determine the role that gap junctions play in the normal and abnormal (i.e., diabetic neuropathy) physiology of bladder and corporal smooth muscle cells, in the Streptozotocin (STZ) and BB/W diabetic rat models. To this end, we will test the following hypotheses: Hypothesis 1: Kinase-mediated (PKC, PKA, PKG, PTK) alterations in junctional conductance and single channel properties will be more pronounced in myocyte cell pairs from control animals than diabetic animals. Further we hypothesize that kinase-mediated increases in macroscopic junctional conductance are a result of channel recruitment in control rats, but in diabetic animals junctional conductance/multichannel activity will remain unchanged. This aim is focused on determining if there are any diabetes-related or organ-specific differences resulting in dynamic kinase-mediated changes in open probability and/or channel recruitment. Hypothesis 2: Phosphorylation via kinases differentially affects permselectivity of gap junctions. Furthermore, the documented affects of diabetes mellitus on kinases will manifest as detectable a|terations in gap junction channel permselectivity/selectivity. If junctional conductance and permselectivity do not change in proportion upon exposure to kinase activators or inhibitors then one can conclude that the selectivity properties have changed and/or changes in open probability/channel recruitment have occurred. Hypothesis 3: Delivery of a second messenger (cAMP, cGMP, IP3) to one cell will affect non-junctional K+ conductances in an adjacent cell via the transit of the messenger through gap junctions. Compare and contrast diabetic and normal animals. These experiments are designed to illustrate the effects of second messenger transfer from cell-to-ceil Further, they will establish whether the gap junction channels are a viable path in effecting resting potentials of cells so linked, and thereby, establish which K channel populations are involved in this process.